A genome-wide association study reported an association of chronic pancreatitis (CP) with variants in PRSS1-PRSS2 (rs10273639; near the gene encoding cationic trypsinogen) and CLDN2-MORC4 loci (rs7057398 in RIPPLY1 and rs12688220 in MORC4).
Those preliminary data suggest low prevalence of SPINK1 and PRSS1 mutations in the Chinese population, generally, as well as in CP patients, indicating that these mutations do not contribute to the development of CP.
The strong association of mutations in the PRSS1 gene and in the SPINKI gene with chronic pancreatitis supports the concept of intracellular trypsin activation as an initiating and extremely important step in the development of pancreatitis.
Two subjects from HP families (including a 93 year old subject with PRSS1R122H without pancreatitis), one with chronic pancreatitis and one with a normal pancreas, were studied.
In 1996, the identification of the first HP-associated mutation in the cationic trypsinogen gene provided a breakthrough in our understanding of the pathogenesis of chronic pancreatitis.
Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease.
R116C mutation of cationic trypsinogen in a Turkish family with recurrent pancreatitis illustrates genetic microheterogeneity of hereditary pancreatitis.
The best characterized misfolding variants in the highly expressed digestive proteases cationic trypsinogen (PRSS1) and carboxypeptidase A1 (CPA1) are strong, causative risk factors for chronic pancreatitis and may be associated with autosomal dominant hereditary pancreatitis.
Children with pathogenic PRSS1 variants progressed more rapidly to CP compared to children without PRSS1 variants (median time to CP: 2.52 vs 4.48 years; P = 0.003).
Mutations in genes encoding cationic trypsinogen (PRSS1), pancreatic secretory trypsin inhibitor (SPINK1) and chymotrypsinogen C (CTRC) are associated with chronic pancreatitis.
Contribution of the CFTR gene, the pancreatic secretory trypsin inhibitor gene (SPINK1) and the cationic trypsinogen gene (PRSS1) to the etiology of recurrent pancreatitis.
Inclusion criteria were the presence of a PRSS1 mutation with pancreatic symptoms or chronic pancreatitis in at least two first-degree relatives or three second-degree relatives without another cause.
Mutations in cationic trypsinogen (PRSS1), cystic fibrosis transmembrane conductance regulator (CFTR), and serine protease inhibitor, Kazal type 1 (SPINK1) genes have been variably associated with both the hereditary and the idiopathic form of chronic pancreatitis (CP).
The strong association of mutations in the PRSS1 gene and in the SPINK1 gene with chronic pancreatitis supports the concept of intracellular trypsin activation as an initiating and extremely important step in the development of pancreatitis.